Initial review by CDC, Malawi and UNC IRBs of Version 1.0 of Protocol (version date: April 16, 2003)

June 9, 2003

The DSMB reviews protocol and recommends that the trial go forward

September 15, 2003*

First version of protocol approved by all 3 IRBs after responses to respective IRB reports

January 12, 2004

Pre-enrolment Study Visit by external monitor

March 10, 2004*

Amendment 1 (version Nov17, 2003) i. Reconcile all recommendations from the 3 IRBs differences in approved protocols across the 3 ruling IRBsii. Include changing the starting the medications to birth instead of 7 days

Amendment 3 (Version Sep 08, 2004) i. Correcting the dose of the second line infant regimen. ii. Adjusting the toxicity table related to neutropenia to account for differences in an African population

February 2, 2005

DSMB reviews data as of Nov 15, 2004

February 7, 2005

Amendment 5 (Version Dec 03, 2004) Notification of Maternal ARV switch from nevirapine to second line drug (nelfinavir) in light of FDA advisory and advisory, and hepatic toxicities. CDC IRB required this notification be labeled an amendment. (Note that amendment 6 reflects the permanent replacement for maternal nevirapine)

March 15, 2005*

Amendment 4 (Version Dec 03, 2004) i. Addition to the maternal antiretroviral (ARV) regimen an extra 7 days to prevent development of nevirapine resistance. ii. Additional follow-up of infants found to be HIV-infected for safety monitoring and development of resistance development.

DSMB meets and recommends stopping enhanced control arm and continuing to randomize to two intervention arms

March 27, 2008

In response to stopping enhanced control arm, the team did the following: i. Notify three IRBs ii. Notify study participants. Those on control arm given choice of switching arms iii. New study participants are read a statement of the findings and told they will only receive the intervention arms iv. CDC GAP, WHO, NICHD, NIAID, ANRS are notified